4,4-dimethyl-4,5-dihydro-3H-pyrazole | 7171-32-6

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: 4,4-dimethyl-4,5-dihydro-3H-pyrazole
• 英文别名: 4,4-dimethyl-4,5-dihydro-3H-pyrazole；4,4-Dimethyl-Δ¹-pyrazolin；4,4-Dimethyl-1-pyrazolin；4,4-Dimethyl-pyrazolin-1；4,4-dimethyl-3,5-dihydropyrazole
• CAS: 7171-32-6
• 化学式: C₅H₁₀N₂
• 分子量: 98.1478
• InChiKey: WJIPRLMEAZGAJT-UHFFFAOYSA-N

物化性质

• 熔点：
  40-42 °C
• 沸点：
  88.3±7.0 °C(Predicted)
• 密度：
  1.01±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  7
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  24.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4,4-dimethyl-4,5-dihydro-3H-pyrazole 以 甲醇 、 乙醇 为溶剂， 反应 4.0h， 生成 N-ethyl-4,4-dimethyl-4,5-dihydro-pyrazole-1-carboximidothioic acid methyl ester
  参考文献：
  名称：

  [EN] SYNTHESIS OF SUBSTITUTED PYRAZOLINE CARBOXAMIDINE DERIVATIVES
  [FR] SYNTHÈSE DE DÉRIVÉS DE PYRAZOLINE CARBOXAMIDINE SUBSTITUÉS

  摘要：

  公开号：

  WO2011092226A8
• 作为产物：
  描述：

  二甲基丙二胺 在 sodium hypochlorite 、 双氧水 作用下， 以 甲醇 、 水 为溶剂， 以59%的产率得到4,4-dimethyl-4,5-dihydro-3H-pyrazole
  参考文献：
  名称：

  N′-(Arylsulfonyl)pyrazoline-1-carboxamidines as Novel, Neutral 5-Hydroxytryptamine 6 Receptor (5-HT₆R) Antagonists with Unique Structural Features

  摘要：

  The 5-HT6 receptor (5-HT6R) has been in the spotlight for several years regarding CNS-related diseases. We set out to discover novel, neutral 5-HT6R antagonists to improve off-target selectivity compared to basic amine-containing scaffolds dominating the field. High-throughput screening identified the N'-(sulfonyl)pyrazoline-1-carboxamidine scaffold as a promising neutral core for starting hit-to-lead. Medicinal chemistry, molecular modeling, small molecule NMR and X-ray crystallography were subsequently applied to optimize the leads into antagonists (compounds 1-49) displaying high 5-HT6R affinity with optimal off-target selectivity. Unique structural features include a pseudoaromatic system and an internal hydrogen bond freezing the bioactive conformation. While physicochemical properties and CNS availability were generally favorable, significant efforts had to be made to improve metabolic stability. The optimized structure 42 is an extremely selective, hERG-free, high-affinity 5-HT6R antagonist showing good human in vitro metabolic stability. Rat pharrnacokinetic data were sufficiently good to enable further in vivo profiling.

  DOI：

  10.1021/jm200466r

文献信息

• [EN] ARYLSULFONYL PYRAZOLINE CARBOXAMIDINE DERIVATIVES AS 5-HT6 ANTAGONISTS<br/>[FR] DÉRIVÉS DE CARBOXAMIDINE DE PYRAZOLINE ARYLSULFONYLIQUE FORMANT DES ANTAGONISTES DE 5-HT6
  申请人：SOLVAY PHARM BV

  公开号：WO2009115515A1

  公开（公告）日：2009-09-24

  This invention concerns arylsulfonyl pyrazoline carboxamidine derivatives as antagonists of 5- HT6 receptors, to methods for the preparation of these compounds and to novel intermediates useful for their synthesis. The invention also relates to the uses of such compounds and compositions, particularly their use in administering them to patients to achieve a therapeutic effect in Parkinson's disease, Huntington's chorea, schizophrenia, anxiety, depression, manic depression, psychoses, epilepsy, obsessive compulsive disorders, mood disorders, migraine, Alzheimer's disease, age related cognitive decline, mild cognitive impairment, sleep disorders, eating disorders, anorexia, bulimia, binge eating disorders, panic attacks, akathisia, attention deficit hyperactivity disorder, attention deficit disorder, withdrawal from abuse of cocaine, ethanol, nicotine or benzodiazepines, pain, disorders associated with spinal trauma or head injury, hydrocephalus, functional bowel disorder, Irritable Bowel Syndrome, obesity and type-2 diabetes. The compounds have the general formula (1) wherein the symbols have the meanings given in the description.

  这项发明涉及芳基磺酰基吡唑啉羧酰胺衍生物作为5-HT6受体拮抗剂，以及用于制备这些化合物的方法和用于它们合成的新型中间体。该发明还涉及这些化合物和组合物的用途，特别是它们在向患者施用以达到在帕金森病、亨廷顿舞蹈症、精神分裂症、焦虑、抑郁症、躁郁症、精神病、癫痫、强迫性障碍、情绪障碍、偏头痛、阿尔茨海默病、与年龄相关的认知下降、轻度认知障碍、睡眠障碍、进食障碍、厌食症、暴食症、暴食症、恐慌发作、不安定症、注意力缺陷多动障碍、注意力缺陷障碍、戒除可卡因、乙醇、尼古丁或苯二氮卓类药物滥用、疼痛、与脊柱损伤或头部损伤相关的障碍、脑积水、功能性肠道障碍、肠易激综合征、肥胖和2型糖尿病中的治疗效果方面的应用。这些化合物具有一般公式（1），其中符号的含义如描述中所示。
• SYNTHESIS OF SUBSTITUTED PYRAZOLINE CARBOXAMIDINE DERIVATIVES
  申请人：van Loevezijn Arnold

  公开号：US20130060041A1

  公开（公告）日：2013-03-07

  This invention relates to organic chemistry, in particular to processes for the preparation of pyrazoline carboxamidine derivatives of formula (I), known as potent 5-HT6 antagonists. The invention also relates to novel intermediates of these compounds. wherein the symbols have the meanings given in the description.

  本发明涉及有机化学，特别是关于制备式(I)的吡唑啉羧酰胺衍生物的过程，这些衍生物被称为有效的5-HT6受体拮抗剂。本发明还涉及这些化合物的新型中间体。其中符号的含义如描述所示。
• Synthesis of substituted pyrazoline carboxamidine derivatives
  申请人：van Loevezijn Arnold

  公开号：US09422244B2

  公开（公告）日：2016-08-23

  This invention relates to organic chemistry, in particular to processes for the preparation of pyrazoline carboxamidine derivatives of formula (I), known as potent 5-HT6 antagonists. The invention also relates to novel intermediates of these compounds. wherein the symbols have the meanings given in the description.

  本发明涉及有机化学，具体涉及制备式（I）的吡唑烷基脲衍生物的方法，其作为有效的5-HT6拮抗剂而知名。本发明还涉及这些化合物的新型中间体，其中符号的含义在说明中给出。
• WO2008/34863
  申请人：——

  公开号：——

  公开（公告）日：——
• ——
  作者：STROEFER E.、 ROHR W.、 ROTERMUND G. W.、 FISCHER R.、 NEUDERT R.

  DOI：——

  日期：——